Peripheral insulin resistance and creatinine levels are associated with plasma phosphorylated tau

Background Type 2 diabetes (T2D) and insulin resistance (IR) are associated with increased dementia risk, but their association with plasma AD biomarkers e.g., plasma phosphorylated tau (pTau) is unknown. Here, we tested the relationship between diabetes, IR, and pTau, as well as considering the influence of comorbid conditions (obesity and kidney disease) on plasma biomarker measurements. Method 425 participants from the Wisconsin Registry for Alzheimer’s Prevention were included based on availability of plasma assays. Plasma pTau181 and pTau231 were measured using a single molecule array (Simoa) assay on Quanterix. Diabetes status at baseline visit was determined using fasting blood glucose and medication usage. IR was measured using the homeostatic model assessment of IR (HOMA2‐IR) and z‐scored. Obesity was indicated through body mass index (BMI) and kidney function was determined by blood creatinine levels. We used Welch’s t‐test to examine differences in pTau levels based on diabetes status. Pearson correlations tested the linear relationships between longitudinal pTau181 and pTau231 with baseline HOMA2‐IR, BMI, and creatinine. Two linear mixed effects models were fitted; one for each of the pTau markers. Each model included random intercepts and age‐related slopes with fixed effects of baseline z‐scored HOMA2‐IR, BMI, and creatinine. Results were considered significant at p